Cyclophosphamide, one of the more useful antitumor agents in current clinical use, is known to be oxidized to 4-hydroxycyclophosphamide/aldophosphamide which subsequently gives rise to phosphoramide mustard. The latter is believed to be the active cytotoxic agent. Conversion to phosphoramide mustard is presumed to occur both within and outside of cells. The relative amount of conversion at each site is not known but may be an important determinant of the antitumor activity and oncotoxic specificity of cyclophosphamide because 4-hydroxycyclophosphamide/aldophosphamide is more potent than is phosphoramide mustard and because the oncotoxic specificity of cyclophosphamide may reside with 4-hydroxycyclophosphamide/aldophosphamide. The objectives of the present investigation are to determine the relative contributions of phosphoramide mustard generated extra- and intracellularly to the antitumor and toxic effects of cyclophosphamide and to demonstrate a way of improving the oncotoxic specificity of cyclophosphamide by selectively neutralizing the phosphoramide mustard generated extracellularly. Sodium thiosulfate will be used to selectively neutralize extracellular phosphoramide mustard. The rat W256 carcinosarcoma and the mouse P388 lymphoma growing in suitable hosts will be used to monitor antitumor activity. Lethality, bone marrow function, and organ (spleen, thymus, bladder) weights will be monitored as indicators of toxicity.